TLR9 polymorphisms are associated with altered IFN-γ levels in children with cerebral malaria

Nadia A. Sam-Agudu, Jennifer A. Greene, Robert O. Opoka, James W. Kazura, Michael J. Boivin, Peter A. Zimmerman, Melissa A. Riedesel, Tracy L. Bergemann, Lisa A Schimmenti, Chandy C. John

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Toll-like receptor (TLR) polymorphisms have been associated with disease severity in malaria infection, but mechanisms for this association have not been characterized. The TLR2, 4, and 9 single nucleotide polymorphism (SNP) frequencies and serum interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels were assessed in Ugandan children with cerebral malaria (CM, N = 65) and uncomplicated malaria (UM, N = 52). The TLR9 C allele at -1237 and G allele at 1174 were strongly linked, and among children with CM, those with the C allele at -1237 or the G allele at 1174 had higher levels of IFN-γ than those without these alleles (P = 0.03 and 0.008, respectively). The TLR9 SNPs were not associated with altered IFN-γ levels in children with UM or altered TNF-α levels in either group. We present the first human data that TLR SNPs are associated with altered cytokine production in parasitic infection.

Original languageEnglish (US)
Pages (from-to)548-555
Number of pages8
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume82
Issue number4
DOIs
StatePublished - Apr 2010

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